Tumour invasion and metastasis initiated by microRNA-10b in breast cancer

Nature 2007 Oct 11; 449 (7160):682-688

Speaker: Wei-Ting Chang（張瑋庭）                                     Date : 2007.12.12

Commentator: Li-Jin Hsu, Ph.D（徐麗君 老師）      Place : Room 601

Abstract

        Metastasis is a complex process by which primary tumor cells invade adjacent tissue, translocation to distant tissue through the circulation system, and finally proliferate from microscopic growths into secondary tumors. In addition, some non-coding genes termed microRNAs (miRNAs) have been implicated in regulating diverse cellular processes that involve oncogenesis and tumor suppression. Recently, many evidences indicated that microRNA can drive the metastatic process by using transcription factors and can execute the initial steps of the invasion-metastasis cascade. However, the role of miRNAs in mediating cancer metastasis is still unknown. In this study, the authors indicated that the metastatic breast cancer cell lines can highly express microRNA-10b (miR-10b), and the expression level of miR-10b is highly correlated with the migration and invasion of the cancer cell lines. Overexpression of miR-10b in the non-metastatic breast cancer lines can cause the robust invasion and metastasis. Twist, a transcription factor, can directly binds to the putative promoter of miR-10b (MIRN10B) then induce the expression of miR-10b. RHOC, a well-characterized pro-metastatic gene, can be suppressed by the expression of HOXD10 (homeobox D10), which can be converted by the twist induced miR-10b expression. MiR-10b expression level is associated with the metastasis outcome in breast cancer patients but not in the primary breast cancer patients. Collectively, the authors’ findings indicate that miR-10b plays a part specifically in the metastatic process but not in primary tumor formation. From the undescribed regulatory pathway, in which a pleiotropic transcription factor induces expression of a specific microRNA, which suppresses its direct target and in turn activates another pro-metastatic gene, leading to tumor cell invasion and metastasis.

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